Possible Interaction: Caffeine and Levodopa

“The ability of orally administered caffeine to modify the antiparkinsonian efficacy of levodopa or piribedil, a putative dopamine receptor agonist, was studied in six patients.”

“At Cox regression models, higher caffeine consumption was associated with a lower rate of starting l-Dopa treatment (HR = 0.630; 95%CI = 0.382-0.996).”

“ Caffeine , the world's most widely used psychomotor stimulant, potentiates the antiparkinsonian effects of levodopa in preclinical models, as noted nearly 40 years ago.[1][1] The findings prompted early placebo-controlled crossover studies of caffeine as an adjunct to levodopa or a dopamine agonist”

“ Caffeine administered before levodopa may improve its pharmacokinetics in some parkinsonian patients.”

“This double-blind, randomized, crossover study revealed that caffeine shortened the maximal plasma concentration of levodopa , decreased the latency to levodopa walking and tapping motor response, and increased the magnitude of walking response.”

“ Caffeine , which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA.”

“Discussion and conclusions Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA , which can potentially impact PD treatment and warrants further investigation.”

“Coadministration of caffeine with a low dose of l-DOPA reduces dyskinesia in animals with striatopallidal knock-out to wild-type levels, suggesting a dependence on adenosine receptor activity.”

“ Caffeine given systemically (15 mg/kg) or into the dorsal striatum or external globus pallidus (GPE; 20–40 μg) increased contralateral forepaw stepping by 14%, 27%, and 26%, respectively, and enhanced the effect of 8 mg/kg L-DOPA on stepping.”

“Cross-sensitization between caffeine and L-dopa following repeated treatment and their positive interaction during chronic co-adminstration in hemiparkinsonian mice suggest that repeated exposure to caffeine may alter L-dopa responses in PD.”

“Furthermore, daily co-administration of caffeine plus L-dopa produced enhanced rotational behavior, compared to caffeine or L-dopa alone, indicating an additive or synergistic interaction between caffeine and L-dopa during repeated treatment.”

“In a cross-challenge paradigm, daily treatment of mice with L-dopa (compared to daily saline) produced a three-fold enhancement in the rotational response to a subsequent re-challenge with caffeine.”

“Similarly, daily treatment of mice with caffeine produced a six-fold enhancement in the rotational response to a subsequent re-challenge with L-dopa.”

“From these and earlier data it is suggested that part of the potentiating effect of caffeine on the L-DOPA induced motility is due to the increased cerebral level of dopamine and part to a catecholamine-receptor sensitizing effect of caffeine.”

“The accumulation of dopamine in the brain, and the levels of DOPA in both brain and plasma following administration of L-DOPA , all increased when caffeine was given beforehand.”

“Administration of SKF 38393 (1.5 mg/kg) or L-3,4-dihydroxyphenyl-alanine (6 mg/kg), but not quinpirole (0.15 mg/kg) or R(−)-propylnorapomorphine (0.01 mg/kg), induced a significantly higher contralateral turning behaviour in rats subchronically treated with caffeine than in vehicle-pretreated rats.”